Bioinformatics Analysis Identifies PLA2G7 as a Key Antigen-Presenting Prognostic Related Gene Promoting...

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Antigen presentation is crucial in cancer immune evasion.
• This study focuses on antigen-presenting prognostic related genes (APPGs) in hepatocellular carcinoma (HCC).

Purpose of the Study:

• To investigate APPGs and their mechanisms in HCC.
• To develop a prognostic score (APP.Score) for HCC patients.
• To explore the role of phospholipase A2, group 7 (PLA2G7) in HCC progression and immune evasion.

Main Methods:

• Constructed APP.Score using nonnegative matrix factorization (NMF), weighted gene co-expression network analysis (WGCNA), random forest (RF), and least absolute shrinkage and selection operator (LASSO).
• Performed in vitro experiments to validate APPG expression and PLA2G7 knockdown effects.
• Analyzed correlations between APP.Score, immune infiltration, immune checkpoint genes, and overall survival (OS).

Main Results:

• APP.Score correlated positively with immune cell infiltration and immune checkpoint genes, and negatively with OS, serving as an independent prognostic factor for HCC.
• High expression of APPGs, including PLA2G7, was associated with lower OS.
• PLA2G7 knockdown suppressed HCC progression, reduced programmed death-ligand 1 (PD-L1) and p-STAT1/STAT1 levels, with PD-L1 reduction reversed by STAT1 activation.

Conclusions:

• APP.Score is a significant independent prognostic factor for HCC.
• PLA2G7 silencing inhibits HCC development and PD-L1 expression, suggesting PLA2G7 as a potential therapeutic target.
• This research offers novel insights into antigen presentation mechanisms and immune evasion in HCC.